Though exercise is a principal cardiorespiratory stress, there is no consensus on the control processes underlying the exercise hyperpnea. However, evidence is accumulating which suggests that the exercise hyperpnea is coupled, in the steady-state, to CO2 flow to the lungs. It is the purpose of this investigation to determine the mechanisms responsible for the ventilatory changes induced by alterations of CO2 flow. I propose to perform definitive experiments which will determine the nature of the stimulus (i.e. chemoreceptive or mechanoreceptive mediation of the ventilatory changes) and the kinetics of the ventilatory response. This will be accomplished by independently altering, in dogs, the two components of CO2 flow: pulmonary blood flow and mixed venous CO2 content. Extracorporeal gas exchange techniques will be utilized to effect square wave elevations and reductions in mixed venous PCO2 while continuously monitoring arterial PCO2 and pH changes via indwelling electrodes. Square wave changes will allow ventilatory kinetics to be analyzed. These studies will emphasize the transient ventilatory and PaCO2 changes to determine if a signal proportional to the CO2 flow might exist in the arterial blood. In another series of studies the mechanism of the hypopnea consequent to diminished pulmonary blood flow will be studied. Two separate perfusion circuits will isolate the systemic circulation from the pulmonary circulation. While maintaining systemic arterial blood gases and perfusion, the ventilatory response to independent alterations in blood flow and CO2 tension in the pulmonary circuit will be assessed. This approach should determine if the ventilatory changes are related to chemoreceptive or mechanoreceptive events and should suggest an afferent pathway. These studies will lead toward a better understanding of ventilatory control processes related to the homeostasis of arterial PCO2 and H ion.